Silveira, CatarinaSousa, Ana CarlaCorredeira, PatríciaMartins, MartaSousa, Ana RitaDa Cruz Paula, ArnaudSelenica, PierBrown, David N.Golkaram, MahdiKaplan, ShannonZhang, ShileLiu, LiWeigelt, BrittaReis-Filho, Jorge S.Costa, LuisCarmo-Fonseca, Maria2023-02-032023-02-032022Biomolecules. 2022 Dec 6;12(12):1818http://hdl.handle.net/10451/56149© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Analysis of cell-free circulating tumor DNA obtained by liquid biopsy is a non-invasive approach that may provide clinically actionable information when conventional tissue biopsy is inaccessible or infeasible. Here, we followed a patient with hormone receptor-positive and human epidermal growth factor receptor (HER) 2-negative breast cancer who developed bone metastases seven years after mastectomy. We analyzed circulating cell-free DNA (cfDNA) extracted from plasma using high-depth massively parallel sequencing targeting 468 cancer-associated genes, and we identified a clonal hotspot missense mutation in the PIK3CA gene (3:178952085, A > G, H1047R) and amplification of the CCND1 gene. Whole-exome sequencing revealed that both alterations were present in the primary tumor. After treatment with ribociclib plus letrozole, the genetic abnormalities were no longer detected in cfDNA. These results underscore the clinical utility of combining liquid biopsy and comprehensive genomic profiling to monitor treatment response in patients with metastasized breast cancer.engCirculating cell-free DNALiquid biopsyMetastatic breast cancerRibociclib plus letrozolejournal article10.3390/biom121218182218-273X